The overarching aim of this competitive renewal (K02) application is to advance my knowledge in genetics and epidemiology, and to acquire specialized skills in quantitative methodology in tandem with completing the research initiated in the first funding cycle pertaining to development and validation of a measure of substance use disorder (SUD) liability. This research has yielded a provisional liability index (LI) for quantifying SUD risk in boys at ages 10-12, 12-14, 16 and 19 and girls at ages 10-12. The LI has been shown to predict SUD between childhood and young adulthood, indicating that it may be practical for detecting high risk youths. Moreover, variation on the LI has been shown to have 79% heritability in a pilot study, indicating that it may also be a heuristic tool in SUD etiology research. Employing item response theory (IRT) methodology, in conjunction with longitudinal multivariate modeling, the provisional LI will be completed up to age 30 in males and up to age 28 in females using the data accrued by the NIDA-funded Center for Education and Drug Abuse Research (CEDAR) where I am Co-PI and Director of the Methodology and Statistics Core. During the next 5 years, the LI will additionally be cross-validated on three large datasets having appropriate item content: 1) the Collaborative Studies on the Genetics of Alcoholism (COGA), 2) the Minnesota Twin Family Study (MTFS), and, 3) the National Epidemiological Survey on Alcohol and Related Conditions. (NESARC). Following the cross-validation studies, the LI will be prepared for computer adaptive test (CAT) administration to complement the paper and pencil version. Conclusion of this task sets the stage for future R01 funding at which time I will conduct a standardization study to derive norms for the final LI versions between childhood and adulthood and to elucidate genetic mechanisms. PUBLIC HEALTH RELEVANCE: Commensurate with the perspective of basic science informing practical application, this project will derive and validate an instrument - the liability index - to quantify SUD risk on a continuous scale ranging from 0-1 based on CEDAR's 19 years of empirical research into SUD etiology. Practical instruments will be developed for use across the main chronological period for detecting youths and young adults who are at high risk for use.